Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cataracts were induced in suckling mice by multiple injections of L-buthionine-S,R-sulfoximine (BSO), a specific inhibitor of GSH biosynthesis, starting on post-natal day 7. The earliest visible lens aberrations began approximately 2 days after t(o), following 99% depletion of lens GSH. Cataract development then proceeded through four stages within less than 24 hr. Elevated Na+ and Ca+ and decreased K+ were first detected in pre-cataractous (stage 0) lenses. During stage 0, lens Na+ and K+ levels displayed a significant inverse correlation; by contrast, Ca2+ levels were poorly correlated with those of Na+. The initial increase in Na+ exceeded the decrease in K+. This suggested the presence of osmotic stress prior to cataract stage 1 (developing floriform). Increased lens hydration was first apparent in stage 1, coincident with a marked elevation of Ca2+, further increase in Na+ and decrease in K+. These trends persisted in the stage 2 cataract (completed floriform). Subsequent changes in lens hydration and cation content during cataract stages 3 (degenerate floriform) and 4 (amorphous translucent) suggested substantial influx of extracellular fluid into the affected lenses. The BSO cataract may represent a useful in vivo model to study the functions of GSH in maintaining normal lens cation balance and transparency.
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PMID:Lens GSH depletion and electrolyte changes preceding cataracts induced by buthionine sulfoximine in suckling mice. 162 47

The ability of transparent and cataractous human, rabbit and mice lenses to metabolize hydrogen peroxide in the surrounding medium was evaluated. Using a chemiluminescence method in a system of luminol-horseradish peroxidase and a photometric technique, the temperature-dependent kinetics of H2O2 decomposition by lenses were measured. The ability of opaque human lenses to catalyze the decomposition of 10(-4) M H2O2 was significantly decreased. However, this was reversed by the addition of GSH to the incubation medium. Incubation of the mice lenses with the initial concentration H2O2 10(-4) M led to partial depletion of GSH in normal and cataractous lenses. Human cataractous lenses showed decreased activities of glutathione reductase, glutathione peroxidase (catalyzing reduction of organic hydroperoxides including hydroperoxides of lipids), superoxide dismutase, but no signs of depletion in activities of catalase or glutathione peroxidase (utilizing H2O2). The findings indicated an impairment in peroxide metabolism of the mature cataractous lenses compared to normal lenses to be resulted from a deficiency of GSH. An oxidative stress induced by accumulation of lipid peroxidation products in the lens membranes during cataract progression could be considered as a primary cause of GSH deficiency and disturbance of the redox balance in the lens.
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PMID:Peroxide-metabolizing systems of the crystalline lens. 173 65

The effect of the instillation of gamma-glutamylcysteinylethyl ester (gamma-GCE), which has been reported to function as a precursor of glutathione, on cataract formation was examined in rats in which diabetes had been induced by Streptozotocin (STZ). Three days after i.p. treatment with 50 mg/kg body weight of STZ, male Wistar rats aged 6 weeks received instillations of gamma-GCE in solution or liposomes prepared with dipalmitoylphosphatidylcholine (DPPC) for a period of 9 weeks. Cataract formation and development were observed by use of a cataract camera every week. After 9 weeks' observation, the lenses were enucleated and the content of the lens GSH was measured. Instillation of gamma-GCE in solution or liposomes to STZ-diabetic rats not only inhibited cataract formation but also kept lens GSH level almost at the control level. In addition, the inhibitory effect of the instillation of gamma-GCE in liposome was stronger than that of gamma-GCE in solution. The present results indicate that the administration of gamma-GCE in solution or in liposomes inhibits diabetic cataract formation, possibly by preventing lens GSH depletion.
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PMID:[The inhibitory effect of gamma-glutamylcysteinylethyl ester (gamma-GCE) instillation on experimental diabetic cataract formation in rats]. 183 18

Glucocorticoid-induced cataract formation appears to proceed via oxidation or peroxidation steps possibly caused by multiple activities of glucocorticoid in the living system. Attempts were made to modify GC-induced metabolic changes and prevent cataract formation using intermediates of the citric acid cycle. The compounds were applied to the embryos at 3, 10 and 20 hr after the administration of hydrocortisone succinate sodium (HC:0.25 mumol/egg) to 15-day-old eggs. At 48 hr after HC treatment the lenses were classified and analyzed. Almost all lenses were classified as stage IV-V (greater than 94%). However, the application of sodium isocitrate (IC:15 mumol/egg) which was the most potent among several intermediates tested showed a significant preventive effect against cataract formation. The administration of IC prevented the decline of GSH, the elevations of LPO and reduced the marked elevation of glucose in the lens caused by HC. The IC treatment also diminished the elevation of LPO in blood and liver. The above effects by IC on HC-induced events may be due to the action of IC in preventing the early decline of hepatic GSH caused by HC. Possibly IC was utilized as an intermediate of the citric acid cycle and a substrate for isocitrate dehydrogenase in cytosol to modify GC-induced metabolic changes.
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PMID:Preventive effect of isocitrate on glucocorticoid-induced cataract formation of developing chick embryo. 191 99

Lens opacities developed within 48-72 hr in mice that received a series of eight injections of L-buthionine sulfoximine, a specific inhibitor of glutathione (GSH) biosynthesis, on postnatal days 8 and 9. Initial histopathologic features consisted of swollen fibers in the central anterior cortex and displacement of cell nuclei from the bow region to the posterior cortex. These aberrations suggest early fiber cell membrane and/or cytoskeletal dysfunction. A massive wave of fiber cell lysis then engulfed the entire lens cortex and nucleus within 24 hr and left only epithelial cells intact, suggesting a concerted mechanism of cataract generation. The acellular core of the mature cataract seen on postnatal day 16 consisted of a granular matrix in which pycnotic and fragmented cell nuclei were located near the terminus of the lens epithelium. The epithelium displayed increased mitotic activity and meridional row disorganization. During the next two weeks, rapid regeneration of lens fibers, displacement of the acellular necrotic cytoplasm to the center and rear of the lens, and vacuole formation were observed. As new fibers were differentiated, partial regeneration of the bow was seen. However, the cataract was irreversible.
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PMID:Rapid deterioration of lens fibers in GSH-depleted mouse pups. 203 11

This study deals with the effects of the SH oxidizing agent diamide (diazene dicarboxylic acid bis-(N,N-dimethyl-amide)) on the water-soluble proteins from rabbit lenses. The dialyzed protein extracts were incubated for 0.5-1.5 h with various concentrations of diamide. Alterations in sulphydryl contents, gel filtration and gel electrophoresis profiles of proteins were recorded. The response to 2 mM diamide treatment for 1 h consists of rapid oxidation (up to 40%) of protein-bound sulphydryl groups accompanied by appearance of polypeptides with apparent molecular weights in excess of 68,000. A protein with a molecular weight of 29 kDa was shown to be specially involved in cross-linking. The linkages in the dialyzed water-soluble lens protein fraction induced by diamide may be reduced by GSH (10 mM) treatment of the protein extract. The main target of oxidative insult induced by diamide in the water-soluble proteins of the lens is probably the superficially localized sulphydryl groups of crystallins. Our observations suggest that this oxidative system of proteins may be a useful tool for cataract research.
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PMID:Diamide-induced cross-linking of the lens water-soluble proteins as a model of the early oxidative changes during senile cataract formation. 208 97

Effects of novel aldose reductase inhibitors, M16209 (1-(3-bromobenzo[b]furan-2-ylsulfonyl)hydantoin) and M16287 (1-(3-chlorobenzo[b]furan-2-ylsulfonyl)hydantoin), on galactose-induced cataract formation in rats were investigated. Rats fed a 30% galactose diet developed lenticular opacity in the peripheral region by the 6th day of galactose feeding and showed gradual progression of opacity from the equator to the center of lenses. Histological study on the 15th day showed apparent lens fiber swelling and vacuolation predominantly in the equatorial and anterior cortical regions. Biochemical changes such as accumulation of galactitol, depletion of myo-inositol and decrease in glutathione (GSH) content in lenses preceded the appearance of opacity. Remarkable increase in NADPH content and decrease in NADP+ content, in addition to elevation of the ratio of Na+/K+, in lenses were also observed on the 15th day. Both M16209 and M16287 (10, 30 and 100 mg/kg/day, p.o.) dose-dependently ameliorated these morphological and biochemical changes except that restoration of myo-inositol content was incomplete. These results indicate that M16209 and M16287 can prevent galactose-induced cataract formation through amelioration of metabolic disorders and thus have high potential for clinical use in the treatment of some diabetic complications.
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PMID:Effects of novel hydantoin derivatives with aldose reductase inhibiting activity on galactose-induced cataract in rats. 212 52

This paper presents an overview of the current state of our knowledge concerning the metabolism and function of glutathione (GSH) in the lens, with particular reference to the contributions of Dr Jin H. Kinoshita to this field. Glutathione in the lens is synthesized from its constituent amino acids and degraded by mechanisms involving transpeptidation and hydrolysis. The turnover of GSH in the lens is due to its catabolism rather than transport of GSSG as is the case in red blood cells and some other tissues. Three aspects of the functional role of GSH in cataract formation are considered. First, GSH may be important in maintaining protein thiols in the reduced state, thus preventing the formation of high molecular weight protein aggregates which are the basis for light scattering and lens opacification. A second function may be to protect membrane -SH groups that are important in cation transport and permeability. A third functional role is to detoxify hydrogen peroxide and other organoperoxides. The glutathione redox cycle is intimately involved in the detoxification of H2O2 which is normally present in the aqueous humor.
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PMID:Glutathione and its function in the lens--an overview. 219 12

In this study we have investigated the oxidative metabolism of red cells (RBC), plasma, serum and aqueous humour of healthy subjects and of age-matched cataractous patients with and without chronic renal failure (CRF). Reduced glutathione (GSH) levels in RBC were lower in CRF patients than in the other groups. Oxidized glutathione (GSSG) plasma levels in CRF patients were higher than those of controls and cataractous subjects. The activity of the enzyme glucose-6-phosphate dehydrogenase in RBC was significantly reduced in CRF patients with respect to the other two groups. The levels of malondialdehyde (MDA) in RBC and in lens were about twice in CRF patients compared with the other two groups. The plasma levels of vitamin E were diminished in CRF patients; on the contrary, the biological liquid oxidant activity (BLOA) of serum in CRF patients was significantly higher than in controls and in cataractous patients without CRF. Cataractous patients with and without CRF showed similar levels of GSH in aqueous humour; on the contrary, the content of GSSG was significantly higher in CRF patients. Our findings seem to demonstrate that CRF patients are exposed to oxidative stresses that could probably act synergistically with uraemia and carbamylation of lens proteins. This synergism could explain why CRF represents a relatively high risk factor for cataract.
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PMID:Systemic human diseases as oxidative risk factors in cataractogenesis. II. Chronic renal failure. 226 73

The study has examined the effects of the SH-oxidizing agent diamide (Diazane dicarboxylic acid bis-(N,N-dimethyl-amide)) on the water-soluble portion of proteins from rabbit lenses. The dialyzed protein extracts were incubated for 1-1.5 hrs with various concentrations of diamide. Treatments were monitored for alterations in sulphydryl contents, gel filtration and gel electrophoresis profiles of proteins. The response to 2 mM diamide treatment for 1 hr consists of rapid oxidation (up to 40%) of protein-bound sulphydryl groups accompanied by an appearance of polypeptides with apparent molecular weights. The protein with molecular weight of 29 kilodaltons was shown to be involved in cross-linking. The linkages in the dialyzed water-soluble lens polypeptide fraction induced by diamide may be reduced by GSH (10 mM) treatment of protein extract. The main target of oxidative insult induced by diamide in the water-soluble proteins of the lens is probably the superficially localized sulphydryl groups of crystallins. Our observations suggest that the described oxidative system of proteins may be a useful tool for cataract research.
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PMID:[Oligomerization of water soluble proteins of rabbit crystalline lens under the action of diamide]. 226 11


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